Further insights into the molecular bases of the lectin-mediated adhesion of oral bacteria to polymorphonuclear leukocytes (PMNs) and the biological implications of these interactions have been acquired. Two PMN glycoprotein receptors, both of which were recognized by the sialic acid reactive lectins of oral streptococci as well as the Gal/GalNAc reactive lectins of actinomyces, have been unequivocally identified. The major receptor is leukosialin (CD43). This glycoconjugate was initially detected by binding of Gal/GalNAc or sialic acid reactive plant lectins and, subsequently, by binding of the actinomyces and streptococci to a 130 kDa band on nitrocellulose transfers of PMN and differentiated HL60 cell extracts separated by SDS-PAGE. Binding of the actinomyces and plant lectins with similar specificities required exposure of the saccharide receptors by sialidase. The 130kDa band was the only glycoprotein detected by an anti-leukosialin antibody. Conclusive evidence of the receptor activity of this glycoconjugate was obtained by bacterial binding to the 130kDa band on transfers of PMN or HL60 cell extracts that were immunoprecipitated with the anti-leukosialin antibody and the immunoprecipitates subjected to SDS-PAGE. In addition, all of the previously described plant lectins recognized a 200 kDa band that was identified as the leukocyte common antigen (CD45). Both bacteria also bound to this glycoconjugate following its concentration from cell extracts by immunoprecipitation, with sialidase requirements identical to those described above. The specificities of all reactions were verified by saccharide inhibition and the failure of mutants or strains lacking the lectin activities to bind to the phagocytic cells or to the glycoconjugates on nitrocellulose transfers. Lectin-dependent interactions of the streptococci with PMNs had major implications for the initiation of endocarditis. A number of oral Streptococcus gordonii strains activated PMNs and were ingested by these phagocytic cells but only two were susceptible to killing. Of major interest was the finding that the strains that resisted lectin-mediated killing by PMNs produced severe endocarditis in a rat model system. In marked contrast, those strains that were killed by the phagocytic cells failed to induce endocarditis. Moreover, the production of endocarditis did not correlate with a number of previously suggested parameters. Thus, resistance to lectin-mediated killing of these bacteria by the phagocytic cells is a determinant of virulence for the initiation of endocarditis by this particular group of streptococci.